The overall aim of this project is to begin development of a novel conformal small-animal irradiator, suitable for studying genetic markers of radiation response and radiobiological models at therapeutic dose levels. There has been a revolution in functional imaging that has coincided with the development of small animal imaging devices, including microCT, microMR, and microSPECT. Many of the institutions that have acquired these devices use them to study the efficacy of molecular markers for the diagnosis, detection, and characterization of cancer. One important component of these studies is the evaluation of response to therapeutic doses of radiation; however, the technology of animal irradiation is crude, making reproducible irradiation of in situ tumors and normal organs difficult. We propose to develop a small animal irradiator (microRT) that delivers customized, conformal dose distributions to rats and mice that are accurately localized, with accurate dosimetry, and conformal therapy treatment planning, to support quantitative molecular imaging studies and radiobiological experiments. The system will be based on high activity, small volume, 192Ir radiation sources, and the radiation delivery will be computer controlled and automated. Our first aim is to design a prototype small-animal irradiator based on an 192Ir source, according to the specifications defined by a multidisciplinary radiobiology and animal imaging research team. Our second aim is to build a prototype irradiator using the source and collimator design developed in SA1. The third aim is to validate that the prototype built in SA2 meets the specifications developed in SA1. The successful completion of these specific aims will open a new field of preclinical micro imaging-guided radiobiology investigations on small animals. [unreadable] [unreadable]